(Newbee)
05-25-04 08:15
No 509509
(Rated as: excellent)
In Vitro Characterization of Ephedrine-Related Stereoisomers at Biogenic Amine Transporters and the Receptorome Reveals Selective Actions as Norepinephrine Transporter Substrates
Richard B. Rothman, Nga Vu, John S. Partilla, Bryan L. Roth, Sandra J. Hufeisen, Beth A. Compton-Toth, Jon Birkes, Richard Young, and Richard A. Glennon
Abstract
Ephedrine is a long-studied stimulant available both as a prescription and over-the-counter medication, as well as an ingredient in widely marketed herbal preparations, and is also used as a precursor for the illicit synthesis of methamphetamine. Ephedrine is related to phenylpropanolamine, a decongestant removed from the market place due to concerns that its use increased the risk of hemorrhagic stroke. Standard pharmacology texts emphasize that ephedrine is both a direct and indirect adrenergic agonist, activating adrenergic receptors both by direct agonist activity as well as by releasing norepinephrine via a carrier-mediated exchange mechanism. Chemically, ephedrine possesses two chiral centers. In the present study, we characterized the stereoisomers of ephedrine and the closely related compounds pseudoephedrine, norephedrine, pseudonorephedrine (cathine), methcathinone, and cathinone at biogenic amine transporters and a large battery of cloned human receptors (e.g., “receptorome”). The most potent actions of ephedrine-type compounds were as substrates of the norepinephrine transporter (EC50 values of about 50 nM) followed by substrate activity at the dopamine transporter. Screening the receptorome demonstrated weak affinity at alpha2-adrenergic and 5-hydroxytryptamine7 receptors (Ki values 1–10 µM) and no significant activity at beta-adrenergic or alpha1-adrenergic receptors. Viewed collectively, these data indicate that the pharmacological effects of ephedrine-like phenylpropanolamines are likely mediated by norepinephrine release, and although sharing mechanistic similarities with, they differ in important respects from those of the phenylpropanonamines methcathinone and cathinone and the phenyisopropylamines methamphetamine and amphetamine.
(Active Asperger Archivist)
05-25-04 09:11
No 509522
makes a good add'n to my digest!
Act quickly or not at all.
(Hive Bee)
05-31-04 04:47
No 510520
Thanks for the providing this article. It was added to Post 506957 (Lego: "Richard A. Glennon: literature collection", General Discourse).
But could you please provide the next time the following information:
In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates
Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA
J. Pharmacol. Exp. Ther., 2003, 307(1), 138-145
Medline (PMID=12954796)
DOI:10.1124/jpet.103.053975
See also Post 425177 (Lilienthal: "Please use the DOI for citations", General Discourse).
Thanks!
The tendency is to push it as far as you can